EP3080634A1 - Zero echo time mr imaging with water/fat separation - Google Patents

Zero echo time mr imaging with water/fat separation

Info

Publication number
EP3080634A1
EP3080634A1 EP14814790.3A EP14814790A EP3080634A1 EP 3080634 A1 EP3080634 A1 EP 3080634A1 EP 14814790 A EP14814790 A EP 14814790A EP 3080634 A1 EP3080634 A1 EP 3080634A1
Authority
EP
European Patent Office
Prior art keywords
readout
magnetic field
space
strength
imaging
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP14814790.3A
Other languages
German (de)
French (fr)
Other versions
EP3080634B1 (en
Inventor
Miha Fuderer
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Koninklijke Philips NV
Original Assignee
Koninklijke Philips NV
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Koninklijke Philips NV filed Critical Koninklijke Philips NV
Priority to EP14814790.3A priority Critical patent/EP3080634B1/en
Publication of EP3080634A1 publication Critical patent/EP3080634A1/en
Application granted granted Critical
Publication of EP3080634B1 publication Critical patent/EP3080634B1/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01RMEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00Arrangements or instruments for measuring magnetic variables
    • G01R33/20Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/48NMR imaging systems
    • G01R33/4828Resolving the MR signals of different chemical species, e.g. water-fat imaging
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01RMEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00Arrangements or instruments for measuring magnetic variables
    • G01R33/20Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/48NMR imaging systems
    • G01R33/4816NMR imaging of samples with ultrashort relaxation times such as solid samples, e.g. MRI using ultrashort TE [UTE], single point imaging, constant time imaging
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01RMEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00Arrangements or instruments for measuring magnetic variables
    • G01R33/20Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/48NMR imaging systems
    • G01R33/4818MR characterised by data acquisition along a specific k-space trajectory or by the temporal order of k-space coverage, e.g. centric or segmented coverage of k-space
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01RMEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00Arrangements or instruments for measuring magnetic variables
    • G01R33/20Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/48NMR imaging systems
    • G01R33/4818MR characterised by data acquisition along a specific k-space trajectory or by the temporal order of k-space coverage, e.g. centric or segmented coverage of k-space
    • G01R33/482MR characterised by data acquisition along a specific k-space trajectory or by the temporal order of k-space coverage, e.g. centric or segmented coverage of k-space using a Cartesian trajectory
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01RMEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00Arrangements or instruments for measuring magnetic variables
    • G01R33/20Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/48NMR imaging systems
    • G01R33/4818MR characterised by data acquisition along a specific k-space trajectory or by the temporal order of k-space coverage, e.g. centric or segmented coverage of k-space
    • G01R33/482MR characterised by data acquisition along a specific k-space trajectory or by the temporal order of k-space coverage, e.g. centric or segmented coverage of k-space using a Cartesian trajectory
    • G01R33/4822MR characterised by data acquisition along a specific k-space trajectory or by the temporal order of k-space coverage, e.g. centric or segmented coverage of k-space using a Cartesian trajectory in three dimensions
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01RMEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00Arrangements or instruments for measuring magnetic variables
    • G01R33/20Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/48NMR imaging systems
    • G01R33/4818MR characterised by data acquisition along a specific k-space trajectory or by the temporal order of k-space coverage, e.g. centric or segmented coverage of k-space
    • G01R33/4824MR characterised by data acquisition along a specific k-space trajectory or by the temporal order of k-space coverage, e.g. centric or segmented coverage of k-space using a non-Cartesian trajectory
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01RMEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00Arrangements or instruments for measuring magnetic variables
    • G01R33/20Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/48NMR imaging systems
    • G01R33/4818MR characterised by data acquisition along a specific k-space trajectory or by the temporal order of k-space coverage, e.g. centric or segmented coverage of k-space
    • G01R33/4824MR characterised by data acquisition along a specific k-space trajectory or by the temporal order of k-space coverage, e.g. centric or segmented coverage of k-space using a non-Cartesian trajectory
    • G01R33/4826MR characterised by data acquisition along a specific k-space trajectory or by the temporal order of k-space coverage, e.g. centric or segmented coverage of k-space using a non-Cartesian trajectory in three dimensions
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01RMEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00Arrangements or instruments for measuring magnetic variables
    • G01R33/20Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/48NMR imaging systems
    • G01R33/483NMR imaging systems with selection of signals or spectra from particular regions of the volume, e.g. in vivo spectroscopy
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01RMEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00Arrangements or instruments for measuring magnetic variables
    • G01R33/20Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/48NMR imaging systems
    • G01R33/483NMR imaging systems with selection of signals or spectra from particular regions of the volume, e.g. in vivo spectroscopy
    • G01R33/4831NMR imaging systems with selection of signals or spectra from particular regions of the volume, e.g. in vivo spectroscopy using B1 gradients, e.g. rotating frame techniques, use of surface coils
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01RMEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00Arrangements or instruments for measuring magnetic variables
    • G01R33/20Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/48NMR imaging systems
    • G01R33/483NMR imaging systems with selection of signals or spectra from particular regions of the volume, e.g. in vivo spectroscopy
    • G01R33/4833NMR imaging systems with selection of signals or spectra from particular regions of the volume, e.g. in vivo spectroscopy using spatially selective excitation of the volume of interest, e.g. selecting non-orthogonal or inclined slices
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01RMEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00Arrangements or instruments for measuring magnetic variables
    • G01R33/20Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/48NMR imaging systems
    • G01R33/483NMR imaging systems with selection of signals or spectra from particular regions of the volume, e.g. in vivo spectroscopy
    • G01R33/4833NMR imaging systems with selection of signals or spectra from particular regions of the volume, e.g. in vivo spectroscopy using spatially selective excitation of the volume of interest, e.g. selecting non-orthogonal or inclined slices
    • G01R33/4835NMR imaging systems with selection of signals or spectra from particular regions of the volume, e.g. in vivo spectroscopy using spatially selective excitation of the volume of interest, e.g. selecting non-orthogonal or inclined slices of multiple slices

Definitions

  • the invention relates to the field of magnetic resonance (MR) imaging. It concerns a method of MR imaging of chemical species having at least two different resonance frequencies.
  • the invention also relates to a MR device and to a computer program to be run on a MR device.
  • Image-forming MR methods which utilize the interaction between magnetic fields and nuclear spins in order to form two-dimensional or three-dimensional images are widely used nowadays, notably in the field of medical diagnostics, because for the imaging of soft tissue they are superior to other imaging methods in many respects, do not require ionizing radiation and are usually not invasive.
  • the body of the patient to be examined is arranged in a strong, uniform magnetic field (Bo field) whose direction at the same time defines an axis (normally the z-axis) of the co-ordinate system on which the measurement is based.
  • the magnetic field produces different energy levels for the individual nuclear spins in dependence on the magnetic field strength which can be excited (spin resonance) by application of an electromagnetic alternating field (RF field, also referred to as Bi field) of defined frequency (so-called Larmor frequency, or MR frequency).
  • RF field electromagnetic alternating field
  • Bi field defined frequency
  • the distribution of the individual nuclear spins produces an overall magnetization which can be deflected out of the state of equilibrium by application of an electromagnetic pulse of appropriate frequency (RF pulse) while the magnetic field extends perpendicular to the z-axis, so that the magnetization performs a precessional motion about the z-axis.
  • the precessional motion describes a surface of a cone whose angle of aperture is referred to as flip angle.
  • the magnitude of the flip angle is dependent on the strength and the duration of the applied electromagnetic pulse.
  • 90° pulse the spins are deflected from the z axis to the transverse plane (flip angle 90°).
  • the magnetization relaxes back to the original state of equilibrium, in which the magnetization in the z direction is built up again with a first time constant T 1 (spin lattice or longitudinal relaxation time), and the
  • the variation of the magnetization can be detected by means of one or more receiving RF coils which are arranged and oriented within an examination volume of the MR device in such a manner that the variation of the magnetization is measured in the direction perpendicular to the z-axis.
  • the decay of the transverse magnetization is accompanied, after application of, for example, a 90° pulse, by a transition of the nuclear spins (induced by local magnetic field inhomogeneity) from an ordered state with the same phase to a state in which all phase angles are uniformly distributed (dephasing).
  • the dephasing can be compensated by means of a refocusing pulse (for example a 180° pulse). This produces an echo signal (spin echo) in the receiving coils.
  • the signal picked up in the receiving coils then contains components of different frequencies which can be associated with different locations in the body.
  • the MR signal data obtained via the RF coils corresponds to the spatial frequency domain and is called k-space data.
  • the k-space data usually includes multiple lines acquired with different phase encoding. Each line is digitized by collecting a number of samples. A set of k-space data is converted to a MR image by means of Fourier transformation or other appropriate reconstruction algorithms.
  • MR imaging of tissues with very short transverse relaxation times, such as bone or lung is becoming increasingly important.
  • Nearly all known methods for this purpose basically employ three-dimensional (3D) radial k-space sampling.
  • ZTE zero echo time
  • a readout gradient is set before excitation of magnetic resonance with a high-bandwidth and thus short, hard RF pulse.
  • gradient encoding starts instantaneously upon excitation of magnetic resonance.
  • the acquisition of a free induction decay (FID) signal starts immediately after radiation of the RF pulse resulting in an effectively zero 'echo time' (TE).
  • FID readout only minimal time is required for setting of the next readout gradient before the next RF pulse can be applied, thus enabling very short repetition times (TR).
  • the readout direction is incrementally varied from repetition to repetition until a spherical volume in k-space is sampled to the required extent. Without the need for switching off the readout gradient between TR intervals, ZTE imaging can be performed virtually silently.
  • a known challenge in ZTE imaging is that the k-space data are slightly incomplete in the k-space center due to the initial dead time that is caused by the finite duration of the RF pulse, transmit-receive switching, and signal filtering.
  • the k-space gap can be addressed, for example, by oversampling of the radial k-space acquisition and/or signal extrapolation.
  • the gap size must be limited to approximately two to three Nyquist dwell times to avoid significant noise amplification as well as deterioration of the spatial response function (see, for example, Weiger et al, Magnetic Resonance in Medicine, 70, 328-332, 2013).
  • the US-patent applicaton US2007/0188172 discloses a near- zero echo time magnetic resonance method which aims at studying objects having very fast spin-spin relaxation rates.
  • water and fat images are generated by either addition or subtraction of the 'in phase' and 'out of phase' datasets, but this approach is rather sensitive to main field inhomogeneities.
  • a chemical encoding based separation of different species is not restricted to water/fat species only. Other species with other chemical shifts could also be considered.
  • the known Dixon-type water/fat separation techniques rely on the acquisition of two or more images by an appropriate (spin) echo sequence such that an echo time value can be attributed to each image, which echo time values in combination with the phasing of the acquired images encode the contributions from water and fat spins.
  • FID signals are acquired in ZTE imaging, as mentioned above, such that the terms 'echo' and 'echo time' have no meaning.
  • the known Dixon techniques are thus not applicable in combination with ZTE imaging.
  • a method of MR imaging of an object positioned in the examination volume of a MR device comprises the steps of:
  • imaging sequence is a zero echo time sequence comprising:
  • the radial ZTE acquisition is principally applied in the conventional fashion.
  • FID signals are acquired as radial k-space samples by rapidly repeating the radiation of RF pulses while the readout direction is gradually varied until a full spherical volume in k-space is sampled.
  • the invention proposes that, as an additional measure, the strength of the readout magnetic field gradient is varied between at least some of the repetitions of the ZTE sequence such that each k-space region is 'visited' during the scan at least two times, each time with a different value of the readout strength.
  • the application of different readout strengths implies that each k-space position is sampled at two or more different sampling times (i.e.
  • the time interval between the RF pulse and the sampling of a given k-space position It is the basic insight of the invention that sampling of each region in k-space with two or more different sampling times in ZTE imaging results in a specific phasing of the acquired FID signals which is induced by the (known) precessional frequency difference of the involved chemical species (e.g. hydrogen in fat and water). This phasing encodes the signal contributions from the different chemical species.
  • the separation of the signal contributions is performed by deriving the individual contributions from the phase differences of the acquired FID signals induced by the variation of the readout strength.
  • the reconstruction and the separation of the signal contributions consists of two steps: (a) estimating a phase map, i.e.
  • Step (b) includes the well-known 'phase unwrapping' problem of Dixon water/fat imaging. Suitable algorithms are well-known and available in existing MR environments. A technique for water/fat separation from MR signals sampled at arbitrary acquisition times, which is principally applicable for the method of invention, is for example described by Eggers et al. (Magnetic Resonance in Medicine, 65, 96-107, 2011).
  • the spherical k-space volume is sampled by randomly varying the readout direction and the readout strength.
  • Compressed sensing may be employed for reconstructing the MR image and/or for separating the signal contributions of the two or more chemical species.
  • the theory of compressed sensing (CS) is known to have a great potential for MR image reconstruction from irregularly sampled k- space data.
  • CS theory a signal data set which has a sparse representation in a transform domain can be recovered from under-sampled measurements by application of a suitable regularisation algorithm. The possibility of under-sampling leads to a significantly reduced acquisition time.
  • CS prescribes the conditions under which a signal data set can be reconstructed exactly or at least with high image quality even in cases in which the k-space sampling density is far below the Nyquist criterion, and it also provides the methods for such reconstruction (see, for example, M. Lustig et al, Magnetic Resonance in Medicine, 58, 1182-1195, 2007).
  • the separation of the signal contributions is performed on the basis of a signal model including at least the MR spectrum of each of the chemical species.
  • a signal model is employed that theoretically describes the acquired FID signals as a function of the respective sampling time (as determined by the applied readout strength).
  • the signal model includes at least the (a-priori known) spectrum of each of the chemical species and the (unknown) spin density.
  • the model may further include the (unknown) spatial variation of the main magnetic field in the examination volume, since the spatial inhomogeneity of the main magnetic field also causes phase shifts of the acquired FID signals which need to be distinguished from the phasing caused by the chemical shift. In the process of MR image reconstruction and separation of the contributions of the different chemical species values of all unknown parameters of the signal model may be sought that best fit the acquired FID signals.
  • a phase map is derived from the acquired FID signals, wherein the inhomogeneity of the main magnetic field is derived from the phase map by exploiting that the phase shift induced by the inhomogeneity of the main magnetic field varies smoothly over space.
  • an ambiguity in the phasing of the FID signals caused by chemical shift and by the inhomogeneity of the main magnetic field may be resolved according to the invention by using prior information.
  • Such prior information may be, for example, that the main magnetic field varies slowly as a function of the spatial coordinates.
  • the readout strength is varied by switching it between two or more pre-selected values between repetitions of the ZTE sequence.
  • This may advantageously be combined with segmented k- space sampling, wherein each segment has the shape of a hollow sphere of a given wall thickness, wherein a different combination of the two or more pre-selected values is applied in sampling of each segment.
  • each k-space position within each segment is sampled at least two times, each time with a different value of the readout strength.
  • a sufficient sampling close to the k-space centre can be accomplished by applying readout magnetic field gradients of low strength for acquisition of the central k-space segments. Higher readout strengths may be applied for the more peripheral segments in order to obtain the desired image resolution.
  • the method of the invention described thus far can be carried out by means of a MR device including at least one main magnet coil for generating a uniform steady magnetic field within an examination volume, a number of gradient coils for generating switched magnetic field gradients in different spatial directions within the examination volume, at least one RF coil for generating RF pulses within the examination volume and/or for receiving MR signals from a body of a patient positioned in the examination volume, a control unit for controlling the temporal succession of RF pulses and switched magnetic field gradients, and a reconstruction unit.
  • the method of the invention is preferably implemented by a corresponding programming of the reconstruction unit and/or the control unit of the MR device.
  • the method of the invention can be advantageously carried out in most MR devices in clinical use at present. To this end it is merely necessary to utilize a computer program by which the MR device is controlled such that it performs the above-explained method steps of the invention.
  • the computer program may be present either on a data carrier or be present in a data network so as to be downloaded for installation in the control unit of the MR device.
  • Figure 1 schematically shows a MR device for carrying out the method of the invention
  • Figure 2 shows a diagram illustrating the ZTE sequence applied according to the invention
  • Figure 3 illustrates the radial sampling of k-space according to an embodiment of the invention using two different readout strengths
  • Figure 4 illustrates the segmented k-space sampling approach of the invention
  • Figures 5 and 6 illustrate an iterative scheme for separating chemical shift from spatial inhomogeneity of the main magnetic field in the image reconstruction step of the method of the invention
  • Figure 7 illustrates random k-space sampling according to a further embodiment of the invention.
  • a MR device 1 which can be used for carrying out the method of the invention is shown.
  • the device comprises superconducting or resistive main magnet coils 2 such that a substantially uniform, temporally constant main magnetic field Bo is created along a z-axis through an examination volume.
  • the device further comprises a set of (1 st , 2 nd , and - where applicable - 3 rd order) shimming coils 2', wherein the current flow through the individual shimming coils of the set 2' is controllable for the purpose of minimizing Bo deviations within the examination volume.
  • a magnetic resonance generation and manipulation system applies a series of RF pulses and switched magnetic field gradients to invert or excite nuclear magnetic spins, induce magnetic resonance, refocus magnetic resonance, manipulate magnetic resonance, spatially and otherwise encode the magnetic resonance, saturate spins, and the like to perform MR imaging.
  • a gradient pulse amplifier 3 applies current pulses to selected ones of whole-body gradient coils 4, 5 and 6 along x, y and z-axes of the
  • a digital RF frequency transmitter 7 transmits RF pulses or pulse packets, via a send-/receive switch 8, to a -body RF coil 9 to transmit RF pulses into the examination volume.
  • a typical MR imaging sequence is composed of a packet of RF pulse segments of short duration which taken together with each other and any applied magnetic field gradients achieve a selected manipulation of nuclear magnetic resonance.
  • the RF pulses are used to saturate, excite resonance, invert magnetization, refocus resonance, or manipulate resonance and select a portion of a body 10 positioned in the examination volume.
  • the MR signals are also picked up by the body RF coil 9.
  • a set of local array RF coils 11, 12, 13 are placed contiguous to the region selected for imaging.
  • the array coils 11, 12, 13 can be used to receive MR signals induced by body-coil RF transmissions.
  • the resultant MR signals are picked up by the body RF coil 9 and/or by the array RF coils 11, 12, 13 and demodulated by a receiver 14 preferably including a preamplifier (not shown).
  • the receiver 14 is connected to the RF coils 9, 11, 12 and 13 via send-/receive switch 8.
  • a host computer 15 controls the current flow through the shimming coils 2' as well as the gradient pulse amplifier 3 and the transmitter 7 to generate a ZTE imaging sequence according to the invention.
  • the receiver 14 receives a plurality of MR data lines in rapid succession following each RF excitation pulse.
  • a data acquisition system 16 performs analog-to-digital conversion of the received signals and converts each MR data line to a digital format suitable for further processing. In modern MR devices the data acquisition system 16 is a separate computer which is specialized in acquisition of raw image data.
  • the digital raw image data is reconstructed into an image representation by a reconstruction processor 17 which applies an appropriate reconstruction algorithm.
  • the MR image represents a a three-dimensional volume.
  • the image is then stored in an image memory where it may be accessed for converting projections or other portions of the image representation into appropriate format for visualization, for example via a video monitor 18 which provides a human-readable display of the resultant MR image.
  • Figure 2 shows a diagram illustrating the ZTE sequence applied according to the invention.
  • the essence of the 'silent' ZTE technique is that excitation RF pulses 20 are transmitted simultaneously with 'frequency-encoding' readout magnetic field gradients G being switched on.
  • the readout magnetic field gradient G is not intended as a slice-selection gradient which implies that the RF pulses 20 have to be extremely short (typically 1 ⁇ s to 8 ⁇ s) in order to achieve sufficient excitation bandwidth.
  • the readout of FID signals takes place during intervals 21 in the presence of the readout magnetic field gradients G
  • the readout magnetic field gradient G has a readout strength and a readout direction both staying substantially constant over each excitation/readout cycle. After each cycle the readout direction is varied only very gradually. The readout direction changes only slightly, e.g. by a few degrees (e.g. 2°). In a practical example, the magnetic field gradient in one spatial direction ramps up from zero to 'full' in about 45 ms. For a full sampling of k-space the readout direction is varied until a spherical volume is covered with sufficient density.
  • a known constraint of the ZTE technique is that there is a finite time between the center of each RF pulse 20 and the start of the sampling interval 21. Depending on the equipment used, this 'dead time' may be anything between 2 ⁇ s and 20 ⁇ s. This means that the center of k-space cannot be scanned. However, it has to be taken into account that the size of the central k-space volume that cannot be sampled depends on the readout strength. The lower the strength of the magnetic field gradient, the smaller is the central k-space region that will not be sampled during the dead time. On the other hand, it is not feasible to apply as weak as possible readout gradients.
  • the strength of the readout magnetic field gradient G is varied between repetitions of the ZTE sequence.
  • This is illustrated in the diagram of Figure 3 showing the interdependence of the k-space position k and the sampling time t (k actually represents three dimensions from which only one is drawn for the purpose of illustration).
  • the application of different readout strengths 'low G' and 'high G' implies that each k-space position is sampled at two or more different sampling times (i.e. the time interval between the RF pulse and the sampling of a given k-space position).
  • the k-space position is 'visited' two times during the scan, namely at
  • Figure 4 illustrates an embodiment of the invention employing a segmented k- space sampling approach, wherein each segment has the shape of a hollow sphere of a given wall thickness, k-space is to be sampled up to The required gradient strength would be (approximately) :
  • is the gyro-magnetic ratio and is the repetition time of the ZTE sequence.
  • FID signals are acquired with the following set of gradient strengths:
  • each segment 1-4 is sampled with a different combination of two different readout strengths. Simultaneously, an optimal coverage of central k-space (segment 4) is achieved.
  • the reconstruction and the water/fat separation consists of two steps: (a) estimating a phase map, i.e. a map reflecting both main magnetic field inhomogeneity and chemical shift effects (and maybe further phase shift-inducing effects), and (b) separating chemical shift from main magnetic field inhomogeneity by the assumption that the latter varies smoothly over space.
  • Step (b) constitutes the well-known 'phase unwrapping' problem of Dixon water/fat imaging. Since suitable algorithms are well-known and available in existing MR environments this does not need to be further elaborated here.
  • Step (a) is performed iteratively.
  • the reconstruction step comprises calculating two sets of information over space: (i) the magnetization density (i.e. the 'water and fat' MR image), and (ii) an estimate of the phase map. At each iteration step, these sets are calculated up to a given resolution (i.e. within a full sphere in k-space).
  • the dashed line in Figure 5 represents the 'average' sampling time for the set of k-space samples of region 2.
  • the phase map is known for the sphere enclosed by region 2 (i.e., regions 4 and 3 in this embodiment). This knowledge is applied in reconstructing region
  • both the magnetization density and the phase map are known, as mentioned before.
  • the signal data can be 'simulated' at any sampling time.
  • simulated data 60 is added in the central k-space region as indicated by the bold dotted lines in Figure 6.
  • the average and the difference are calculated.
  • Transforming the average and the difference to the spatial domain enables calculation of high-resolution (i.e. including region 2) estimates of the magnetization density and the phase map.
  • this process is performed including region 1, and the reconstruction step (a) is accomplished.
  • step (b) the separation of chemical shift from main magnetic field inhomogeneity can be performed in step (b), as mentioned above, by the assumption that the latter varies smoothly over space.
  • Algorithms known in the art for Dixon water/fat imaging may be employed for reconstructing separate water and fat images from the magnetization density and the (inhomogeneity-corrected) phase map.
  • the gradient coils along the x, y and z-axes are controlled such that the readout strengths in the respective directions assume mutually independent random values between repetitions of the ZTE sequence, with the 'noise' being frequency- restricted to about 15 Hz or less, in order not to be audible.
  • FID signals are acquired, with a typical duration of each cycle of one millisecond. After, e.g., 200 seconds of scan time, 200.000 FID signals are available, acquired with a distribution of readout directions and readout strengths.
  • the diagram of Figure 7 shows the sampling time t in relation to the tangential component in k-space for a given radius
  • the central dashed line represents the 'average sampling time' or 'reference sample time'
  • Each of the dots in the diagram represents a FID signal having its characteristic sampling time t at the moment of reaching The
  • resulting data can be considered as comprising a few million points, each with its
  • the component (a) of estimating the phase map is focused on in the following.
  • a region size in k-space is defined such that it can be made sure that it includes, in most cases, at least two points with substantially different values of t.
  • This reconstruction may be performed using a compressed sensing approach.
  • a further three- dimensional image is reconstructed from the data points As a next step

Landscapes

  • Physics & Mathematics (AREA)
  • High Energy & Nuclear Physics (AREA)
  • Condensed Matter Physics & Semiconductors (AREA)
  • General Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Optics & Photonics (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Magnetic Resonance Imaging Apparatus (AREA)

Abstract

The invention relates to a method of MR imaging of an object positioned in an examination volume of a MR device (1), the method comprises the steps of: - subjecting the object (10) to an imaging sequence of RF pulses (20) and switched magnetic field gradients(G), which imaging sequence is a zero echo time sequence comprising: i) setting a readout magnetic field gradient (G) having a readout direction and a readout strength; ii) radiating a RF pulse (20) in the presence of the readout magnetic field gradient (G); iii) acquiring a FID signal in the presence of the readout magnetic field gradient (G), wherein the FID signal represents a radial k-space sample; iv) gradually varying the readout direction; v) sampling a spherical volume in k-space by repeating steps i) through iv) a number of times, with the readout strength being varied between repetitions; - reconstructing a MR image from the acquired FID signals, wherein signal contributions of two or more chemical species to the acquired FID signals are separated. It is an object of the invention to enable silent ZTE imaging in combination with water/fat separation. This is achieved by varying the readout strength such that each position in k-space is sampled at least two times, each time with a different value of the readout strength. Moreover, the invention relates to a MR device and to a computer program for a MR device.

Description

Zero echo time MR imaging with water/fat separation
FIELD OF THE INVENTION
The invention relates to the field of magnetic resonance (MR) imaging. It concerns a method of MR imaging of chemical species having at least two different resonance frequencies. The invention also relates to a MR device and to a computer program to be run on a MR device.
BACKGROUND OF THE INVENTION
Image-forming MR methods which utilize the interaction between magnetic fields and nuclear spins in order to form two-dimensional or three-dimensional images are widely used nowadays, notably in the field of medical diagnostics, because for the imaging of soft tissue they are superior to other imaging methods in many respects, do not require ionizing radiation and are usually not invasive.
According to the MR method in general, the body of the patient to be examined is arranged in a strong, uniform magnetic field (Bo field) whose direction at the same time defines an axis (normally the z-axis) of the co-ordinate system on which the measurement is based. The magnetic field produces different energy levels for the individual nuclear spins in dependence on the magnetic field strength which can be excited (spin resonance) by application of an electromagnetic alternating field (RF field, also referred to as Bi field) of defined frequency (so-called Larmor frequency, or MR frequency). From a macroscopic point of view the distribution of the individual nuclear spins produces an overall magnetization which can be deflected out of the state of equilibrium by application of an electromagnetic pulse of appropriate frequency (RF pulse) while the magnetic field extends perpendicular to the z-axis, so that the magnetization performs a precessional motion about the z-axis. The precessional motion describes a surface of a cone whose angle of aperture is referred to as flip angle. The magnitude of the flip angle is dependent on the strength and the duration of the applied electromagnetic pulse. In the case of a so-called 90° pulse, the spins are deflected from the z axis to the transverse plane (flip angle 90°).
After termination of the RF pulse, the magnetization relaxes back to the original state of equilibrium, in which the magnetization in the z direction is built up again with a first time constant T1 (spin lattice or longitudinal relaxation time), and the
magnetization in the direction perpendicular to the z direction relaxes with a second time constant T2 (spin-spin or transverse relaxation time). The variation of the magnetization can be detected by means of one or more receiving RF coils which are arranged and oriented within an examination volume of the MR device in such a manner that the variation of the magnetization is measured in the direction perpendicular to the z-axis. The decay of the transverse magnetization is accompanied, after application of, for example, a 90° pulse, by a transition of the nuclear spins (induced by local magnetic field inhomogeneity) from an ordered state with the same phase to a state in which all phase angles are uniformly distributed (dephasing). The dephasing can be compensated by means of a refocusing pulse (for example a 180° pulse). This produces an echo signal (spin echo) in the receiving coils.
In order to realize spatial resolution in the body, linear magnetic field gradients extending along the three main axes are superposed on the uniform magnetic field, leading to a linear spatial dependency of the spin resonance frequency. The signal picked up in the receiving coils then contains components of different frequencies which can be associated with different locations in the body. The MR signal data obtained via the RF coils corresponds to the spatial frequency domain and is called k-space data. The k-space data usually includes multiple lines acquired with different phase encoding. Each line is digitized by collecting a number of samples. A set of k-space data is converted to a MR image by means of Fourier transformation or other appropriate reconstruction algorithms.
MR imaging of tissues with very short transverse relaxation times, such as bone or lung, is becoming increasingly important. Nearly all known methods for this purpose basically employ three-dimensional (3D) radial k-space sampling. In the so-called zero echo time (ZTE) technique a readout gradient is set before excitation of magnetic resonance with a high-bandwidth and thus short, hard RF pulse. In this way, gradient encoding starts instantaneously upon excitation of magnetic resonance. The acquisition of a free induction decay (FID) signal starts immediately after radiation of the RF pulse resulting in an effectively zero 'echo time' (TE). After the FID readout, only minimal time is required for setting of the next readout gradient before the next RF pulse can be applied, thus enabling very short repetition times (TR). The readout direction is incrementally varied from repetition to repetition until a spherical volume in k-space is sampled to the required extent. Without the need for switching off the readout gradient between TR intervals, ZTE imaging can be performed virtually silently. A known challenge in ZTE imaging is that the k-space data are slightly incomplete in the k-space center due to the initial dead time that is caused by the finite duration of the RF pulse, transmit-receive switching, and signal filtering. The k-space gap can be addressed, for example, by oversampling of the radial k-space acquisition and/or signal extrapolation. However, the gap size must be limited to approximately two to three Nyquist dwell times to avoid significant noise amplification as well as deterioration of the spatial response function (see, for example, Weiger et al, Magnetic Resonance in Medicine, 70, 328-332, 2013). Further, the US-patent applicaton US2007/0188172 discloses a near- zero echo time magnetic resonance method which aims at studying objects having very fast spin-spin relaxation rates.
In MR imaging, it is often desired to obtain information about the relative contribution of different chemical species, such as water and fat, to the overall signal, either to suppress the contribution of some of them or to separately or jointly analyze the contribution of all of them. It is well-known that these contributions can be calculated if information from two or more corresponding echoes, acquired at different echo times, is combined. This may be considered as chemical shift encoding, in which an additional dimension, the chemical shift dimension, is defined and encoded by acquiring a couple of images at slightly different echo times. In particular for water-fat separation, these types of experiments are often referred to as Dixon-type of measurements. The water-fat separation is possible because there is a known precessional frequency difference of hydrogen in fat and water. In its simplest form, water and fat images are generated by either addition or subtraction of the 'in phase' and 'out of phase' datasets, but this approach is rather sensitive to main field inhomogeneities. However, such a chemical encoding based separation of different species is not restricted to water/fat species only. Other species with other chemical shifts could also be considered.
The known Dixon-type water/fat separation techniques rely on the acquisition of two or more images by an appropriate (spin) echo sequence such that an echo time value can be attributed to each image, which echo time values in combination with the phasing of the acquired images encode the contributions from water and fat spins. However, FID signals are acquired in ZTE imaging, as mentioned above, such that the terms 'echo' and 'echo time' have no meaning. The known Dixon techniques are thus not applicable in combination with ZTE imaging. SUMMARY OF THE INVENTION
From the foregoing it is readily appreciated that there is a need for an improved method of ZTE imaging. It is an object of the invention to enable 'silent' ZTE imaging in combination with water/fat separation.
In accordance with the invention, a method of MR imaging of an object positioned in the examination volume of a MR device is disclosed. The method of the invention comprises the steps of:
subjecting the object to an imaging sequence of RF pulses and switched magnetic field gradients, which imaging sequence is a zero echo time sequence comprising:
i) setting a readout magnetic field gradient having a readout direction and a readout strength;
ii) radiating a RF pulse in the presence of the readout magnetic field gradient;
iii) acquiring a FID signal in the presence of the readout magnetic field gradient, wherein the FID signal represents a radial k-space sample;
iv) gradually varying the readout direction;
v) sampling a spherical volume in k-space by repeating steps i) through iv) a number of times, with the readout strength being varied between repetitions;
reconstructing a MR image from the acquired FID signals, wherein signal contributions of two or more chemical species to the acquired FID signals are separated.
According to the invention, the radial ZTE acquisition is principally applied in the conventional fashion. FID signals are acquired as radial k-space samples by rapidly repeating the radiation of RF pulses while the readout direction is gradually varied until a full spherical volume in k-space is sampled. The invention proposes that, as an additional measure, the strength of the readout magnetic field gradient is varied between at least some of the repetitions of the ZTE sequence such that each k-space region is 'visited' during the scan at least two times, each time with a different value of the readout strength. The application of different readout strengths implies that each k-space position is sampled at two or more different sampling times (i.e. the time interval between the RF pulse and the sampling of a given k-space position). It is the basic insight of the invention that sampling of each region in k-space with two or more different sampling times in ZTE imaging results in a specific phasing of the acquired FID signals which is induced by the (known) precessional frequency difference of the involved chemical species (e.g. hydrogen in fat and water). This phasing encodes the signal contributions from the different chemical species. According to the invention, the separation of the signal contributions is performed by deriving the individual contributions from the phase differences of the acquired FID signals induced by the variation of the readout strength. Preferably, the reconstruction and the separation of the signal contributions consists of two steps: (a) estimating a phase map, i.e. a map reflecting at least main magnetic field inhomogeneity and chemical shift effects (and maybe further phase shift-inducing effects, such as the susceptibility distribution within the imaged object), and (b) separating chemical shift from main magnetic field inhomogeneity by the assumption that the latter varies smoothly over space. Step (b) includes the well-known 'phase unwrapping' problem of Dixon water/fat imaging. Suitable algorithms are well-known and available in existing MR environments. A technique for water/fat separation from MR signals sampled at arbitrary acquisition times, which is principally applicable for the method of invention, is for example described by Eggers et al. (Magnetic Resonance in Medicine, 65, 96-107, 2011).
It has to be noted in this context that the approach of the invention does not necessarily require that exactly each k-space position is sampled at two or more different sampling times. It is sufficient that a certain distribution of k-space positions and sampling times is achieved in order to enable chemical shift separation.
In a preferred embodiment of the invention, the spherical k-space volume is sampled by randomly varying the readout direction and the readout strength. Compressed sensing may be employed for reconstructing the MR image and/or for separating the signal contributions of the two or more chemical species. The theory of compressed sensing (CS) is known to have a great potential for MR image reconstruction from irregularly sampled k- space data. In CS theory, a signal data set which has a sparse representation in a transform domain can be recovered from under-sampled measurements by application of a suitable regularisation algorithm. The possibility of under-sampling leads to a significantly reduced acquisition time. As a mathematical framework for signal sampling and reconstruction, CS prescribes the conditions under which a signal data set can be reconstructed exactly or at least with high image quality even in cases in which the k-space sampling density is far below the Nyquist criterion, and it also provides the methods for such reconstruction (see, for example, M. Lustig et al, Magnetic Resonance in Medicine, 58, 1182-1195, 2007).
In a further preferred embodiment of the invention, the separation of the signal contributions is performed on the basis of a signal model including at least the MR spectrum of each of the chemical species. A signal model is employed that theoretically describes the acquired FID signals as a function of the respective sampling time (as determined by the applied readout strength). The signal model includes at least the (a-priori known) spectrum of each of the chemical species and the (unknown) spin density. The model may further include the (unknown) spatial variation of the main magnetic field in the examination volume, since the spatial inhomogeneity of the main magnetic field also causes phase shifts of the acquired FID signals which need to be distinguished from the phasing caused by the chemical shift. In the process of MR image reconstruction and separation of the contributions of the different chemical species values of all unknown parameters of the signal model may be sought that best fit the acquired FID signals.
According to a preferred embodiment of the invention, a phase map is derived from the acquired FID signals, wherein the inhomogeneity of the main magnetic field is derived from the phase map by exploiting that the phase shift induced by the inhomogeneity of the main magnetic field varies smoothly over space. In other words, an ambiguity in the phasing of the FID signals caused by chemical shift and by the inhomogeneity of the main magnetic field may be resolved according to the invention by using prior information. Such prior information may be, for example, that the main magnetic field varies slowly as a function of the spatial coordinates.
According to a further preferred embodiment of the invention, the readout strength is varied by switching it between two or more pre-selected values between repetitions of the ZTE sequence. This may advantageously be combined with segmented k- space sampling, wherein each segment has the shape of a hollow sphere of a given wall thickness, wherein a different combination of the two or more pre-selected values is applied in sampling of each segment. In this way, by appropriately matching the values of the readout strength and the segmentation of k-space, it can be achieved, that each k-space position within each segment is sampled at least two times, each time with a different value of the readout strength. Simultaneously, a sufficient sampling close to the k-space centre can be accomplished by applying readout magnetic field gradients of low strength for acquisition of the central k-space segments. Higher readout strengths may be applied for the more peripheral segments in order to obtain the desired image resolution.
The method of the invention described thus far can be carried out by means of a MR device including at least one main magnet coil for generating a uniform steady magnetic field within an examination volume, a number of gradient coils for generating switched magnetic field gradients in different spatial directions within the examination volume, at least one RF coil for generating RF pulses within the examination volume and/or for receiving MR signals from a body of a patient positioned in the examination volume, a control unit for controlling the temporal succession of RF pulses and switched magnetic field gradients, and a reconstruction unit. The method of the invention is preferably implemented by a corresponding programming of the reconstruction unit and/or the control unit of the MR device.
The method of the invention can be advantageously carried out in most MR devices in clinical use at present. To this end it is merely necessary to utilize a computer program by which the MR device is controlled such that it performs the above-explained method steps of the invention. The computer program may be present either on a data carrier or be present in a data network so as to be downloaded for installation in the control unit of the MR device.
BRIEF DESCRIPTION OF THE DRAWINGS
The enclosed drawings disclose preferred embodiments of the present invention. It should be understood, however, that the drawings are designed for the purpose of illustration only and not as a definition of the limits of the invention. In the drawings:
Figure 1 schematically shows a MR device for carrying out the method of the invention;
Figure 2 shows a diagram illustrating the ZTE sequence applied according to the invention;
Figure 3 illustrates the radial sampling of k-space according to an embodiment of the invention using two different readout strengths;
Figure 4 illustrates the segmented k-space sampling approach of the invention;
Figures 5 and 6 illustrate an iterative scheme for separating chemical shift from spatial inhomogeneity of the main magnetic field in the image reconstruction step of the method of the invention;
Figure 7 illustrates random k-space sampling according to a further embodiment of the invention.
DETAILED DESCRIPTION OF THE EMBODIMENTS
With reference to Figure 1 , a MR device 1 which can be used for carrying out the method of the invention is shown. The device comprises superconducting or resistive main magnet coils 2 such that a substantially uniform, temporally constant main magnetic field Bo is created along a z-axis through an examination volume. The device further comprises a set of (1st, 2nd, and - where applicable - 3rd order) shimming coils 2', wherein the current flow through the individual shimming coils of the set 2' is controllable for the purpose of minimizing Bo deviations within the examination volume.
A magnetic resonance generation and manipulation system applies a series of RF pulses and switched magnetic field gradients to invert or excite nuclear magnetic spins, induce magnetic resonance, refocus magnetic resonance, manipulate magnetic resonance, spatially and otherwise encode the magnetic resonance, saturate spins, and the like to perform MR imaging.
More specifically, a gradient pulse amplifier 3 applies current pulses to selected ones of whole-body gradient coils 4, 5 and 6 along x, y and z-axes of the
examination volume. A digital RF frequency transmitter 7 transmits RF pulses or pulse packets, via a send-/receive switch 8, to a -body RF coil 9 to transmit RF pulses into the examination volume. A typical MR imaging sequence is composed of a packet of RF pulse segments of short duration which taken together with each other and any applied magnetic field gradients achieve a selected manipulation of nuclear magnetic resonance. The RF pulses are used to saturate, excite resonance, invert magnetization, refocus resonance, or manipulate resonance and select a portion of a body 10 positioned in the examination volume. The MR signals are also picked up by the body RF coil 9.
For generation of MR images of limited regions of the body 10 by means of parallel imaging, a set of local array RF coils 11, 12, 13 are placed contiguous to the region selected for imaging. The array coils 11, 12, 13 can be used to receive MR signals induced by body-coil RF transmissions.
The resultant MR signals are picked up by the body RF coil 9 and/or by the array RF coils 11, 12, 13 and demodulated by a receiver 14 preferably including a preamplifier (not shown). The receiver 14 is connected to the RF coils 9, 11, 12 and 13 via send-/receive switch 8.
A host computer 15 controls the current flow through the shimming coils 2' as well as the gradient pulse amplifier 3 and the transmitter 7 to generate a ZTE imaging sequence according to the invention. The receiver 14 receives a plurality of MR data lines in rapid succession following each RF excitation pulse. A data acquisition system 16 performs analog-to-digital conversion of the received signals and converts each MR data line to a digital format suitable for further processing. In modern MR devices the data acquisition system 16 is a separate computer which is specialized in acquisition of raw image data.
Ultimately, the digital raw image data is reconstructed into an image representation by a reconstruction processor 17 which applies an appropriate reconstruction algorithm. The MR image represents a a three-dimensional volume. The image is then stored in an image memory where it may be accessed for converting projections or other portions of the image representation into appropriate format for visualization, for example via a video monitor 18 which provides a human-readable display of the resultant MR image.
Figure 2 shows a diagram illustrating the ZTE sequence applied according to the invention. The essence of the 'silent' ZTE technique is that excitation RF pulses 20 are transmitted simultaneously with 'frequency-encoding' readout magnetic field gradients G being switched on. The readout magnetic field gradient G is not intended as a slice-selection gradient which implies that the RF pulses 20 have to be extremely short (typically 1 μs to 8 μs) in order to achieve sufficient excitation bandwidth. The readout of FID signals takes place during intervals 21 in the presence of the readout magnetic field gradients G
immediately after the RF pulses 20. Each interval 21 has a duration between 100 and 3 ms. The readout magnetic field gradient G has a readout strength and a readout direction both staying substantially constant over each excitation/readout cycle. After each cycle the readout direction is varied only very gradually. The readout direction changes only slightly, e.g. by a few degrees (e.g. 2°). In a practical example, the magnetic field gradient in one spatial direction ramps up from zero to 'full' in about 45 ms. For a full sampling of k-space the readout direction is varied until a spherical volume is covered with sufficient density.
A known constraint of the ZTE technique is that there is a finite time between the center of each RF pulse 20 and the start of the sampling interval 21. Depending on the equipment used, this 'dead time' may be anything between 2 μs and 20 μs. This means that the center of k-space cannot be scanned. However, it has to be taken into account that the size of the central k-space volume that cannot be sampled depends on the readout strength. The lower the strength of the magnetic field gradient, the smaller is the central k-space region that will not be sampled during the dead time. On the other hand, it is not feasible to apply as weak as possible readout gradients.
According to the invention, the strength of the readout magnetic field gradient G is varied between repetitions of the ZTE sequence. This is illustrated in the diagram of Figure 3 showing the interdependence of the k-space position k and the sampling time t (k actually represents three dimensions from which only one is drawn for the purpose of illustration). The application of different readout strengths 'low G' and 'high G' implies that each k-space position is sampled at two or more different sampling times (i.e. the time interval between the RF pulse and the sampling of a given k-space position). As can be seen in Figure 3, the k-space position is 'visited' two times during the scan, namely at
(using readout strength 'high G') and at (using readout strength 'low G'). The sampling of each k-space position with two or more different sampling times results in a specific phasing of the acquired FID signals which is induced by the precessional frequency difference of, e.g., hydrogen in fat and water. This is exploited in accordance with the invention to separate the signal contributions from fat and water as in the per se known 'phase unwrapping' techniques applied in Dixon-type MR imaging.
Figure 4 illustrates an embodiment of the invention employing a segmented k- space sampling approach, wherein each segment has the shape of a hollow sphere of a given wall thickness, k-space is to be sampled up to The required gradient strength would be (approximately) :
wherein γ is the gyro-magnetic ratio and is the repetition time of the ZTE sequence. This
value will be referred to as:
A variable a is introduced:
wherein is the dead time during which no signal acquisition is possible. A typical
value of a is 5. In this embodiment of the invention, FID signals are acquired with the following set of gradient strengths:
Mathematically, this is an infinite series. However, in practice acquisition may be stopped beyond One additional acquisition should be performed with
G=0. It has to be noted that this proceeding does not result in a large number of extra acquisitions in comparison to a conventional ZTE scan (employing only acquisitions with Considering the required sampling density of the inner k-space spheres of the proposed segmentation, only a limited number of additional radial k-space samples need to be acquired. Hence, the total number of required cycles of the ZTE sequence may be only about twice the number of cycles in a conventional ZTE scan with comparable imaging parameters.
As can be seen in Figure 4, each segment 1-4 is sampled with a different combination of two different readout strengths. Simultaneously, an optimal coverage of central k-space (segment 4) is achieved. One might easily increase the number of readout strengths per segment, for example by choosing and starting at
With reference to Figures 5 and 6 an iterative scheme for separating chemical shift from main magnetic field inhomogeneity in the image reconstruction step of the method of the invention is explained in the following.
In this embodiment, the reconstruction and the water/fat separation consists of two steps: (a) estimating a phase map, i.e. a map reflecting both main magnetic field inhomogeneity and chemical shift effects (and maybe further phase shift-inducing effects), and (b) separating chemical shift from main magnetic field inhomogeneity by the assumption that the latter varies smoothly over space. Step (b) constitutes the well-known 'phase unwrapping' problem of Dixon water/fat imaging. Since suitable algorithms are well-known and available in existing MR environments this does not need to be further elaborated here.
Step (a) is performed iteratively. The reconstruction step comprises calculating two sets of information over space: (i) the magnetization density (i.e. the 'water and fat' MR image), and (ii) an estimate of the phase map. At each iteration step, these sets are calculated up to a given resolution (i.e. within a full sphere in k-space).
It is assumed that initially estimates of the above two sets of information are available for a small central region of k-space region. In the embodiment shown in Figure 5, both magnetization density and the phase map are assumed to be known for regions 4 and 3 (indicated by the bold horizontal line 50 at t=0). As a next step of the iteration, estimates are to be computed including region 2.
The dashed line in Figure 5 represents the 'average' sampling time for the set of k-space samples of region 2. The phase map is known for the sphere enclosed by region 2 (i.e., regions 4 and 3 in this embodiment). This knowledge is applied in reconstructing region
2. Both datasets of region 2 are reconstructed as if they were acquired using the 'average'
(dashed) timing of k-space sampling, for example by using a segmented homogeneity correction method (see Douglas C. Noll et al., IEEE Transactions on Medical Imaging, 10,
629-637, 1991). For this purpose, it is useful to sub-segment region 2 into regions 2a, ... 2d, as depicted in Figure 5. In this way, some distortion caused by magnetic field inhomogeneity is intentionally left in the data. The data reconstructed up to this point behaves as if it were acquired with the sampling timing shown in Figure 6.
For the central k-space region, both the magnetization density and the phase map are known, as mentioned before. Hence, the signal data can be 'simulated' at any sampling time. In this way, simulated data 60 is added in the central k-space region as indicated by the bold dotted lines in Figure 6. From these two data sets, the average and the difference, are calculated. Transforming the average and the difference to the spatial domain enables calculation of high-resolution (i.e. including region 2) estimates of the magnetization density and the phase map. In the next step, this process is performed including region 1, and the reconstruction step (a) is accomplished. The iteration may start by estimating a 0-th order estimate of the phase map from the G=0 k-space sample, which can be considered as the most central 'region' in k-space.
On this basis, the separation of chemical shift from main magnetic field inhomogeneity can be performed in step (b), as mentioned above, by the assumption that the latter varies smoothly over space. Algorithms known in the art for Dixon water/fat imaging may be employed for reconstructing separate water and fat images from the magnetization density and the (inhomogeneity-corrected) phase map.
Another embodiment of the invention is in the following discussed with reference to Figure 7.
In this embodiment, the gradient coils along the x, y and z-axes are controlled such that the readout strengths in the respective directions assume mutually independent random values between repetitions of the ZTE sequence, with the 'noise' being frequency- restricted to about 15 Hz or less, in order not to be audible. FID signals are acquired, with a typical duration of each cycle of one millisecond. After, e.g., 200 seconds of scan time, 200.000 FID signals are available, acquired with a distribution of readout directions and readout strengths.
The diagram of Figure 7 shows the sampling time t in relation to the tangential component in k-space for a given radius The central dashed line represents the 'average sampling time' or 'reference sample time' Each of the dots in the diagram represents a FID signal having its characteristic sampling time t at the moment of reaching The
resulting data can be considered as comprising a few million points, each with its
characteristic values of kx, ky, kz and t. Their (complex) values are with i being the index of the point.
For the step of reconstruction and water/fat separation, again the component (a) of estimating the phase map is focused on in the following.
A region size in k-space is defined such that it can be made sure that it includes, in most cases, at least two points with substantially different values of t. For each
point,
is calculated. Herein, should be read as 'neighborhood of and should be read as
'point present in neighborhood'. In essence, can be interpreted as 'density-compensated data-point'.
Further, is calculated as
which can be interpreted as 'signal weighted by the difference of the actual sampling time of the data point and the average sampling time in the neighborhood, normalized over the local variance of the sampling time'. In essence, it represents the slope of the signal with respect to sampling time.
As a next step is calculated as
which provides an estimate of how much the signal deviates from what it would have been if it had been measured at
A three-dimensional image is reconstructed from the difference
This reconstruction may be performed using a compressed sensing approach. A further three- dimensional image is reconstructed from the data points As a next step
is calculated, wherein i is the imaginary unit and γ is the gyro -magnetic ratio. The result is a direct estimate of the phase map (in units of Tesla). On this basis, again, the separation of chemical shift from main magnetic field inhomogeneity can be performed by assuming that the latter varies smoothly over space, and per se known algorithms can then be employed for reconstructing separate water and fat images.

Claims

CLAIMS:
1. Method of MR imaging of an object positioned in an examination volume of a MR device (1), the method comprising the steps of:
subjecting the object (10) to an imaging sequence of RF pulses (20) and switched magnetic field gradients (G), which imaging sequence is a zero echo time sequence comprising:
i) setting a readout magnetic field gradient (G) having a readout direction and a readout strength;
ii) radiating a RF pulse (20) in the presence of the readout magnetic field gradient (G);
iii) acquiring a FID signal in the presence of the readout magnetic field gradient (G), wherein the FID signal represents a radial k-space sample;
iv) gradually varying the readout direction;
v) sampling a spherical volume in k-space by repeating steps i) through iv) a number of times, with the readout strength being varied between repetitions; wherein the readout strength is varied such that individual positions in k-space are sampled at least two times, each time with a different value of the readout strength, such that said k-space position is sampled at two or more different sampling times and
reconstructing a MR image from the acquired FID signals, wherein signal contributions of two or more chemical species to the acquired FID signals are separated.
2. Method of MR imaging according to claim 1, wherein the signal contributions of the two or more chemical species to the FID signals are derived from phase differences of the acquired FID signals induced by the variation of the readout strength.
3. Method of any one of claims lor 2, wherein the separation of the signal contributions is performed on the basis of a signal model including at least the MR spectrum of each of the chemical species.
4. Method of claim 3, wherein the signal model further includes the
inhomogeneity of the main magnetic field in the examination volume.
5. Method of claim 4, wherein a phase map is derived from the acquired FID signals, wherein the inhomogeneity of the main magnetic field is derived from the phase map by exploiting that the phase shift induced by the inhomogeneity of the main magnetic field varies smoothly over space.
6. Method of any one of claims lto 5, wherein the readout strength is varied by switching it between two or more pre-selected values.
7. Method of claim 6, wherein k-space is sampled in a segmented fashion, each segment having the shape of a hollow sphere of a given wall thickness, wherein a different combination of the two or more pre-selected values is applied in sampling of each segment.
8. Method of any one of claims lto 7, wherein the spherical k-space volume is sampled by randomly varying the readout direction and the readout strength.
9. Method of any one of claims lto 8, wherein compressed sensing is employed for reconstructing the MR image and/or for separating the signal contributions of the two chemical species.
10. MR device comprising at least one main magnet coil (2) for generating a uniform, steady magnetic field within an examination volume, a number of gradient coils (4, 5, 6) for generating switched magnetic field gradients (G) in different spatial directions within the examination volume, at least one RF coil (9) for generating RF pulses within the examination volume and/or for receiving MR signals from an object (10) positioned in the examination volume, a control unit (15) for controlling the temporal succession of RF pulses and switched magnetic field gradients, and a reconstruction unit (17), wherein the MR device (1) is arranged to perform the following steps:
subjecting the object (10) to an imaging sequence of RF pulses (20) and switched magnetic field gradients (G), which imaging sequence is a zero echo time sequence comprising:
i) setting a readout magnetic field gradient (G) having a readout direction and a readout strength;
ii) radiating a RF pulse (20) in the presence of the readout magnetic field gradient (G);
iii) acquiring a FID signal in the presence of the readout magnetic field gradient (G), wherein the FID signal represents a radial k-space sample;
iv) incrementally varying the readout direction;
v) sampling a spherical volume in k-space by repeating steps i) through iv) a number of times, with the readout strength being varied between repetitions wherein the readout strength is varied such that individual positions in k-space are sampled at least two times, each time with a different value of the readout strength, such that said k-space position is sampled at two or more different sampling times and;
reconstructing a MR image from the acquired FID signals, wherein signal contributions of two or more chemical species to the acquired FID signals are separated.
11. Computer program to be run on a MR device, which computer program comprises instructions for:
generating an imaging sequence of RF pulses (20) and switched magnetic field gradients (G), which imaging sequence is a zero echo time sequence comprising:
i) setting a readout magnetic field gradient (G) having a readout direction and a readout strength;
ii) radiating a RF pulse (20) in the presence of the readout magnetic field gradient;
iii) acquiring a FID signal in the presence of the readout magnetic field gradient, wherein the FID signal represents a radial k-space sample;
iv) incrementally varying the readout direction;
v) sampling a spherical volume in k-space by repeating steps i) through iv) a number of times, with the readout strength being varied between repetitions wherein the readout strength is varied such that individual positions in k-space is sampled at least two times, each time with a different value of the readout strength,such that said k-space position is sampled at two or more different sampling times and;
reconstructing a MR image from the acquired FID signals, wherein signal contributions of two or more chemical species to the acquired FID signals are separated.
EP14814790.3A 2013-12-12 2014-12-08 Zero echo time mr imaging with water/fat separation Active EP3080634B1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP14814790.3A EP3080634B1 (en) 2013-12-12 2014-12-08 Zero echo time mr imaging with water/fat separation

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP13196868 2013-12-12
PCT/EP2014/076802 WO2015086476A1 (en) 2013-12-12 2014-12-08 Zero echo time mr imaging with water/fat separation
EP14814790.3A EP3080634B1 (en) 2013-12-12 2014-12-08 Zero echo time mr imaging with water/fat separation

Publications (2)

Publication Number Publication Date
EP3080634A1 true EP3080634A1 (en) 2016-10-19
EP3080634B1 EP3080634B1 (en) 2021-04-21

Family

ID=49759134

Family Applications (1)

Application Number Title Priority Date Filing Date
EP14814790.3A Active EP3080634B1 (en) 2013-12-12 2014-12-08 Zero echo time mr imaging with water/fat separation

Country Status (5)

Country Link
US (1) US10094898B2 (en)
EP (1) EP3080634B1 (en)
JP (1) JP6356809B2 (en)
CN (1) CN105814449B (en)
WO (1) WO2015086476A1 (en)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9664761B2 (en) * 2013-06-26 2017-05-30 Medimagemetric LLC Joint estimation of chemical shift and quantitative susceptibility map using MRI signal
EP3191862B1 (en) * 2014-09-12 2021-05-12 Koninklijke Philips N.V. Zero echo time mr imaging
DE102015202062A1 (en) * 2015-02-05 2016-08-11 Siemens Healthcare Gmbh Reconstruction of magnetic resonance image data for multiple chemical species in multi-echo imaging
EP3236277B1 (en) 2016-04-18 2021-12-01 Centre Hospitalier Universitaire Vaudois (CHUV) Differentiated tissue excitation by mri using binomial off-resonance 1-1 rf pulses
US10088539B2 (en) 2016-04-22 2018-10-02 General Electric Company Silent multi-gradient echo magnetic resonance imaging
EP3413070A1 (en) 2017-06-09 2018-12-12 Koninklijke Philips N.V. Dual-echo dixon-type water/fat separation mr imaging
CN107167752B (en) * 2017-07-04 2020-11-24 南京拓谱医疗科技有限公司 Ultra-fast magnetic resonance water-fat separation imaging method
EP3579009A1 (en) * 2018-06-05 2019-12-11 Koninklijke Philips N.V. Zero echo time mr imaging with water-fat separation
US10969451B1 (en) * 2019-09-23 2021-04-06 GE Precision Healthcare LLC Systems and methods for in-phase zero echo time magnetic resonance imaging

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6037772A (en) 1998-01-06 2000-03-14 Arch Development Corp. Fast spectroscopic imaging system
US6332088B1 (en) * 1998-11-12 2001-12-18 Toshiba America Mri, Inc. Method and apparatus for imaging instruments during interventional MRI using asymmetric spin echo sequences
US20010054898A1 (en) * 1999-03-10 2001-12-27 Andrew Li Magnetic resonance imaging compensated for very rapid variations in static magnetic field
JP4251763B2 (en) * 2000-08-11 2009-04-08 株式会社日立メディコ Magnetic resonance imaging system
US6879156B1 (en) 2002-05-17 2005-04-12 The General Hospital Corporation Reducing dead-time effect in MRI projection
US7425828B2 (en) * 2005-10-11 2008-09-16 Regents Of The University Of Minnesota Frequency swept excitation for magnetic resonance
EP1946137A1 (en) * 2005-10-11 2008-07-23 Steady State Imaging Advanced MRI Technologies Frequency swept excitation for magnetic resonance
US7602184B2 (en) 2007-04-30 2009-10-13 The Regents Of The University Of California Magnetic resonance spectroscopic imaging with short echo times
US9341691B2 (en) 2008-11-12 2016-05-17 Regents Of The University Of Minnesota Short TE 3D radial sampling sequence for MRI
US8427147B2 (en) * 2009-04-10 2013-04-23 Wisconsin Alumni Research Foundation Magnetic resonance imaging with fat suppression by combining phase rotating data with phase shifted data in K-space
US9880243B2 (en) * 2011-06-20 2018-01-30 Regents Of The University Of Minnesota Sideband processing for magnetic resonance
US9504851B2 (en) * 2011-06-27 2016-11-29 Koninklijke Philips N.V. Magnetic resonance imaging of bone tissue
EP2610632A1 (en) * 2011-12-29 2013-07-03 Koninklijke Philips Electronics N.V. MRI with Dixon-type water/fat separation and prior knowledge about inhomogeneity of the main magnetic field
EP2648014A1 (en) * 2012-04-03 2013-10-09 Koninklijke Philips N.V. MR imaging using APT contrast enhancement and sampling at multiple echo times
US10156625B2 (en) * 2013-08-12 2018-12-18 Koninklijke Philips N.V. MR imaging with B1 mapping
US10222437B2 (en) * 2013-10-21 2019-03-05 Koninklijke Philips N.V. MR imaging with temperature mapping

Also Published As

Publication number Publication date
CN105814449B (en) 2019-04-30
EP3080634B1 (en) 2021-04-21
US20160313421A1 (en) 2016-10-27
CN105814449A (en) 2016-07-27
US10094898B2 (en) 2018-10-09
JP6356809B2 (en) 2018-07-11
JP2016539735A (en) 2016-12-22
WO2015086476A1 (en) 2015-06-18

Similar Documents

Publication Publication Date Title
EP3080634B1 (en) Zero echo time mr imaging with water/fat separation
US9733328B2 (en) Compressed sensing MR image reconstruction using constraint from prior acquisition
JP5547800B2 (en) MR imaging using parallel signal acquisition
EP3191862B1 (en) Zero echo time mr imaging
JP6416413B2 (en) MR imaging method, MR device, and computer program
US10175322B2 (en) Zero echo time MR imaging with sampling of K-space center
CN107810425B (en) Eliminating non-T2Weighting the T of the signal contribution2Weighted MR imaging
US11360172B2 (en) Zero echo time MR imaging with water-fat separation
WO2012140543A1 (en) Mri of chemical species having different resonance frequencies using an ultra-short echo time sequence
EP2581756A1 (en) MR imaging using parallel signal acquisition
US20220229139A1 (en) Multi-echo mr imaging with spiral acquisition

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20160712

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

AX Request for extension of the european patent

Extension state: BA ME

DAX Request for extension of the european patent (deleted)
RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: KONINKLIJKE PHILIPS N.V.

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: GRANT OF PATENT IS INTENDED

INTG Intention to grant announced

Effective date: 20201119

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE PATENT HAS BEEN GRANTED

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 602014076846

Country of ref document: DE

Ref country code: IE

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: AT

Ref legal event code: REF

Ref document number: 1385190

Country of ref document: AT

Kind code of ref document: T

Effective date: 20210515

REG Reference to a national code

Ref country code: GB

Ref legal event code: 746

Effective date: 20210602

REG Reference to a national code

Ref country code: DE

Ref legal event code: R084

Ref document number: 602014076846

Country of ref document: DE

REG Reference to a national code

Ref country code: LT

Ref legal event code: MG9D

REG Reference to a national code

Ref country code: AT

Ref legal event code: MK05

Ref document number: 1385190

Country of ref document: AT

Kind code of ref document: T

Effective date: 20210421

REG Reference to a national code

Ref country code: NL

Ref legal event code: MP

Effective date: 20210421

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: HR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210421

Ref country code: NL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210421

Ref country code: LT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210421

Ref country code: FI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210421

Ref country code: BG

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210721

Ref country code: AT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210421

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210821

Ref country code: GR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210722

Ref country code: LV

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210421

Ref country code: NO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210721

Ref country code: PT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210823

Ref country code: PL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210421

Ref country code: ES

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210421

Ref country code: RS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210421

Ref country code: SE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210421

REG Reference to a national code

Ref country code: DE

Ref legal event code: R097

Ref document number: 602014076846

Country of ref document: DE

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: RO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210421

Ref country code: SM

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210421

Ref country code: SK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210421

Ref country code: CZ

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210421

Ref country code: DK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210421

Ref country code: EE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210421

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

26N No opposition filed

Effective date: 20220124

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210821

Ref country code: AL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210421

REG Reference to a national code

Ref country code: DE

Ref legal event code: R119

Ref document number: 602014076846

Country of ref document: DE

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MC

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210421

Ref country code: IT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210421

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

GBPC Gb: european patent ceased through non-payment of renewal fee

Effective date: 20211208

REG Reference to a national code

Ref country code: BE

Ref legal event code: MM

Effective date: 20211231

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20211208

Ref country code: IE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20211208

Ref country code: GB

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20211208

Ref country code: DE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20220701

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: FR

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20211231

Ref country code: BE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20211231

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LI

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20211231

Ref country code: CH

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20211231

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: HU

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT; INVALID AB INITIO

Effective date: 20141208

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: CY

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210421

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210421

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: TR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210421

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20210421